escAPe study

Switzerland (ICTRP)

Identifiant de l'essai ICTRP
NCT06277336 (ICTRP)

Titre officiel (approuvé par le comité d'éthique)
Effects of Intravenous [Pyr1]apelin-13 in Healthy Volunteers with Artificially Induced SIAD and Patients with SIAD – a monocentric randomized double-blind placebo-controlled cross-over study - the escAPe Study (BASEC)

Titre académique
Effects of Intravenous [Pyr1]Apelin-13 on Healthy Volunteers With Artificially Induced SIAD- the ESCAPE Study (ICTRP)

Titre public
Effects of Intravenous [Pyr1]Apelin-13 on Healthy Volunteers With Artificially Induced SIAD (ICTRP)

Maladie en cours d'investigation
SIAD - Syndrome of Inappropriate AntidiuresisHyponatremia (ICTRP)

Intervention étudiée
Drug: PlaceboDrug: Apelin Low DoseDrug: Apelin High DoseDrug: Selected Apelin Dose (ICTRP)

Type d'essai
Interventional (ICTRP)

Plan de l'étude
Allocation: Non-Randomized. Intervention model: Crossover Assignment. Primary purpose: Treatment. Masking: Double (Participant, Care Provider). (ICTRP)

Critères d'inclusion/exclusion
Healthy Volunteers:

Inclusion Criteria:

- Informed consent as documented by signature

- Age 18 to 65 years

- Serum sodium level 135-145mmol/l

- Clinically euvolemic status

- For female only: Due to the influence of estrogen on apelin levels, only females
with combined (=containing estrogen) oral contraceptive pill will be included in
order to guarantee a similar estrogen levels at each visit.

Exclusion Criteria:

- Known or suspected allergy to trial product or related products or history of
multiple and/or severe allergic reaction to drugs (including study drugs) or food

- Pregnancy, wish to become pregnant during study period or breastfeeding

- Overt cardiovascular disease or abnormality in screening ECG

- Family history of sudden cardiac death or unexplained sudden death < 50 years

- Known genetic predisposition to cancer (e.g., BRCA, MEN, Lynch syndrome) or personal
history/active malignant disease

- Hepatic impairment (ALAT/ASAT >3x upper limit) or liver cirrhosis

- Kidney disease (GFR < 60ml/min)

- History of epileptic seizures

- Diabetes mellitus type 1 or 2

- Other severe disease requiring regular medication intake or regular medical care

- Any daily medication (including vitamin supplements).

- Uncontrolled hypertension (systolic blood pressure >160mmHg or diastolic blood
pressure >100 mmHg)

- BMI <18 or >29kg/m2

- Inability to follow the procedures of the study (e.g. due to language problems,
psychological disorders, dementia).

- Participation in another study with an investigational drug within the 30 days
preceding and during the present study.

Chronic SIAD patients:

Inclusion Criteria:

- Age = 18 years

- Previous documented diagnosis of chronic SIAD

- Confirmed diagnosis of SIAD at screening visit defined as:

- Plasma sodium concentration < 135 mmol/L (indirect measurement in lithium
heparin plasma

- Plasma osmolality < 300 mOsm/kg

- Urine osmolality > 100 mOsm/kg

- Urine sodium concentration > 30mmol/l

- Clinical euvolemia, defined as an absence of signs of hypovolemia (orthostasis,
tachycardia, decreased skin turgor, dry mucous membranes) or hypervolemia
(edema, ascites)

Exclusion Criteria:

- Known or suspected allergy to trial product or related products or history of
multiple and/or severe allergic reaction to drugs (including study drugs) or food.

- Pregnancy, wish to become pregnant during study period or breastfeeding

- Overt cardiovascular disease or abnormality in screening ECG

- Other potential endocrine cause of hyponatraemia:

- Untreated glucocorticoid deficiency (Defined as morning serum cortisol levels <
300 nmol/l or serum cortisol levels < 450 nmol/l after synacthen test, in
context of compatible clinical examination and medical history)

- Untreated severe hypothyroidism (TSH > 20 mIU/L and/or free T4 < 6 pmol/L)

- Family history of sudden cardiac death or unexplained sudden death < 50 years

- Known genetic predisposition to cancer (e.g., BRCA, MEN, Lynch syndrome, ...) or
personal history/active malignant disease

- Hepatic impairment (ALAT/ASAT > 3x upper limit) or liver cirrhosis

- Kidney disease (GFR < 60ml/min)

- History of epileptic seizures

- Diabetes mellitus type 1 or 2

- Severe immunosuppression defined as leukocytes < 2G

- End of life care

- Severe symptomatic hyponatremia in need of treatment with 3% NaCl-solution or in
need of intensive/intermediate care treatment at time of inclusion

- Risk factors for osmotic demyelination syndrome: hypokalemia (K < 3,4 mmol/L),
malnutrition, advanced liver disease, alcoholism.

- Treatment with a diuretic, a SGLT2 inhibitor or a corresponding combined
preparation, lithium chloride, urea, vaptans, demeclocycline or NSAIDS in the 7 days
before screening (aspirin may be continued).

- Uncontrolled hypertension (systolic blood pressure > 160mmHg or diastolic blood
pressure > 100 mmHg)

- BMI < 18 or > 29kg/m2

- Inability to follow the procedures of the study, e.g. due to language problems,
psychological disorders, dementia, etc. of the participant

- Participation in another study with investigational drug within the 30 days
preceding and during the present study (ICTRP)

non disponible

Critères d'évaluation principaux et secondaires
Total urinary excretion (ml) (ICTRP)

Hourly and total urinary excretion (ml);Change in electrolyte free water clearance (ml/min);Change in free water clearance (ml/min);Change in plasma osmolality (mOsm/kg);Change in plasma sodium (mmol/l);Change in body weight (kg) (ICTRP)

Date d'enregistrement
non disponible

Inclusion du premier participant
non disponible

Sponsors secondaires
non disponible

Contacts supplémentaires
Mirjam Christ-Crain, Prof. Dr.;Sven Lustenberger, MD.;Mirjam Christ-Crain, Prof. Dr., sven.lustenberger@usb.ch; Mirjam.Christ-Crain@usb.ch, +41 61 328 62 64;+41 61 328 70 80, University Hospital Basel, Endocrinology, Diabetes and Metabolism, (ICTRP)

ID secondaires
2023-01716, kt23ChristCrain3 (ICTRP)

Résultats-Données individuelles des participants
non disponible

Informations complémentaires sur l'essai
https://clinicaltrials.gov/ct2/show/NCT06277336 (ICTRP)